insulin

Altered expression of S100 fused-type proteins in human skin due to ultraviolet B irradiation.

Makino Teruhiko T

Ultraviolet B (UVB) radiation profoundly affects epidermal homeostasis by inducing DNA damage, reactive oxygen species generation, and stress signalling. This review summarizes recent findings on the dynamic regulation of S100 fused-type proteins, including filaggrin (FLG), filaggrin 2 (FLG2), cornulin (CRNN), repetin (RPTN), hornerin (HRNR), trichohyalin (TCHH), and trichohyalin like protein 1 (TCHHL1) in human skin after UVB irradiation. In experiments using human skin xenografts, UVB (500 mJ/cm²) irradiation transiently upregulates proliferation-related proteins (TCHHL1, RPTN, and HRNR) and barrier-related proteins (CRNN, FLG2, and FLG) within two days, with normalization by day 7. These temporal changes correlate with activation of the ERK/p38 MAPK and STAT3 pathways, suggesting the existence of a coordinated regulatory network linking proliferation and differentiation during barrier repair. Altered expression in S100 fused-type proteins may serve as biomarkers of acute UVB responses and as targets for promoting epidermal recovery after photodamage.

Methodological Considerations in the Bioequivalence Assessment of Recombinant Human Serum Albumin [Letter].

Chang Peng P, Shen Danfeng D

Centriolar Protein POC5 Regulates Human Adipogenesis and Cellular Senescence: Insights From a Novel Metabolic Ciliopathy.

Pistorio Valeria V, Vatier Camille C, Capel Émilie É, Beaupère Carine C et al.

Centrosomes and primary cilia regulate cellular processes, including microtubule organization and lineage-specific differentiation. POC5, a core component of the centriolar inner scaffold, has been linked to syndromic ciliopathies, yet its role in adipose biology remains unclear. This study investigates the impact of POC5 deficiency on ciliary organization, cellular senescence, adipogenesis, and insulin signaling. To this end, we analyzed primary dermal fibroblasts from a patient carrying a novel homozygous p.(Gln206Ter) POC5 variant and performed mechanistic evaluations in human adipose stem cells (ASCs) with CRISPR-Cas9-mediated POC5 knockout. Centriolar architecture was examined using Ultrastructure Expansion Microscopy (U-ExM), and cellular phenotypes were assessed through proliferation, senescence, and signaling analyses. POC5-deficient fibroblasts showed marked disruption of centriolar architecture, including absent or abnormal primary cilia and supernumerary centrioles. These defects were associated with a 35% decrease in proliferation and a premature senescence, evidenced by increased SA-β-gal activity and upregulation of p-p53, p16, and p21. Moreover, insulin signaling was impaired, with reduced phosphorylation of IRβ, AKT, and ERK1/2. These phenotypes were recapitulated in POC5-KO ASCs, which additionally exhibited a near complete block of adipogenic differentiation, associated with downregulation of PPARγ, C/EBPα, and SREBP1c. Overall, POC5 deficiency promotes insulin resistance and premature senescence, and impaired adipogenesis. These findings identify POC5-related disease as a centrosomal metabolic disorder and highlight the importance of centriolar integrity in systemic energy homeostasis, supporting the need for metabolic monitoring in individuals with POC5 pathogenic variants.

Insulin Clearance Along the Liver-Kidney Axis: Implications for Insulin Action.

Perdomo Germán G, Cózar-Castellano Irene I, Najjar Sonia M SM

The pleiotropic actions of insulin are mediated by cascades of signaling pathways and are regulated by circulating insulin levels. Under physiologic conditions, insulin levels reflect the balance between pancreatic beta-cell secretion and insulin clearance, which occurs primarily in liver hepatocytes and, to a lesser extent, in kidney proximal tubule cells. Therefore, coordination between insulin secretion and clearance is essential for systemic insulin sensitivity. Whereas insulin secretion is widely investigated, exploring the role of insulin clearance in regulating insulin sensitivity remains limited. This review summarizes the main mechanisms underlying insulin clearance along the liver-kidney axis and discusses how they contribute to metabolic regulation in health and disease.